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Understanding Infertility

It was in October 1978, 36 years ago, that the world’s first 'test tube' baby was born, in Manchester. Consultant gynaecologist Patrick Steptoe and research physiologist Robert Edwards were pioneering the technique.

Baby Louise was to be the first of now more than five million babies born all over the world through assisted reproductive technology. From developing a better understanding of it through history, to conducting world leading research in the laboratory, the impact of infertility has captivated the attention of several students and researchers at Oxford.

Dealing with infertility in a deeply religious community

One of the students focusing on the historical and social side of infertility is Marisa Benoit, who is finishing her DPhil in History this year. Her thesis focuses on how infertility was dealt with in Puritan communities who had migrated from the UK to the New England colonies in the mid-17th century.

Marisa, who was able to study at Oxford thanks to support from various donors, began her research expecting something different from what she found. ‘I thought of the Puritan stereotype and that, being deeply religious, Puritans would regard infertile women as inherently sinful,’ she says. ‘But I was surprised to find the amount of sympathy towards women who couldn’t have children, as well as the amount of information on male infertility. I always thought they would just blame the women, but my research revealed that infertility was often regarded as a problem shared by couples.’

Medical knowledge at the time was centred on humours. ‘These were four kinds of fluids in your body, and the balance of these humours regulated your health, including your prospective fertility,’ explains Marisa. Her research explores the connections between ideas about order within the body and the Puritans’ religious and social beliefs about correctly ordered households and communities organised in a ‘godly’ manner.

The ‘right way to be barren’

But even though they set up homes in this fertile landscape and lived in godly-ordered households, women did not always bear children. In these situations, religion provided guidance on how to behave. ‘Just like there was a right way to want children, there was the right way to be a barren woman. Early modern medical ideas about infertility were shaped by Biblical examples and also reflected in popular literature from the period.’

In her research, Marisa found that many of the issues that couples struggle with today were experienced similarly in these 17th-century communities. ‘The personal disappointment, frustration and tensions infertility can cause within relationships also appear in early modern sources,’ she says. Marisa argues that it is best to understand early modern attitudes by examining the idea of a ‘spectrum of infertility’. ‘There were distinctions made between irreversible infertility and episodic infertility, as well as many types of reproductive failure, including multiple miscarriages or stillbirths. Infertility wasn’t hopeless and there were different actions – whether it be prayer or natural remedies to reorder the body – that one could try to fix the problem.’

Improving the effectiveness of IVF

Even though some of the medical ideas of today were already present then, clinical knowledge on how to deal with infertility has certainly moved on, as Dr Dagan Wells and his research group demonstrate. They have developed a new technology that increases the likelihood of success using in-vitro fertilisation (IVF) treatment. Recently, this technique made the transition from research into the clinic, leading to births of several healthy children in the US. The test is now set to be offered in the UK, beginning in January 2015.

In each IVF cycle, several eggs are collected from the ovaries and fertilised. Doctors then have to decide which of the embryos should be transferred to the mother’s womb. The choice is usually made based upon how ‘healthy’ each embryo looks, but this is a relatively poor guide to embryo viability.

Another way of making this choice, pioneered by the team led by Dr Wells, is through chromosome screening. It has been known for more than 20 years that many human embryos contain lethal chromosome abnormalities. ‘As technical advances have continued, we’re now able to look at all of the chromosomes in the embryo, which is a much better guide to their viability than previous methods,’ explains Dr Wells. ‘It’s important to say that these tests are not improving the embryo in any way; they are simply helping to guide us to which of the embryos has the best chance of producing a baby after IVF.’

The technology most commonly used for chromosome screening all over the world is called micro-array comparative genomic hybridisation and typically adds between £2,000 and £3,000 to each IVF cycle. ‘It works really well, but it comes at an appreciable cost, so our plan is to try and deliver the same sort of information in a less expensive way’.

Dr Wells’s research group lived up to this expectation and, with support from the Oxford Biomedical Research Centre (part of the National Institute for Health Research), developed a new technique that can do just that, based upon a technology known as next generation sequencing. ‘It’s a very powerful genetic technology that gives us the capability to look at many embryos simultaneously and therefore share the expense of the analysis over many patients, essentially lowering the cost of the test,’ he explains. The new technology is being made available to all IVF clinics in the UK through Dr Wells’s laboratory.

Making better IVF accessible to all

However, the new technique isn’t yet available on the NHS, neither is any kind of chromosome screening in IVF cycles. But this may be about to change, as a randomised controlled trial to test the next generation sequencing technology began earlier this year. This study should provide conclusive data on the effectiveness of the technique in terms of improving the number of successful IVF cycles. Dr Wells believes that the NHS will find the test cost-effective: ‘Fewer procedures involving the transfer of embryos to the mother will be needed in order to obtain a baby, there will be fewer miscarriages and also fewer instances of children affected by severe chromosome disorders, all of which could lead to cost savings for the NHS.’

This technology will also help scientists get a more in-depth understanding of why IVF cycles fail. This might lead to a further boost in pregnancy rate through IVF. ‘We are trying to understand what causes the failure of those other embryos, the ones that look ok under the microscope and have the right number of chromosomes,’ explains Dr Wells. ‘I think we are just at the cusp of a new understanding of the early embryo, which will lead to important advances in the treatment of infertility.’